On November 06, 2015 Calithera Biosciences, Inc. (Nasdaq:CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, reported it will announce preclinical data today for its lead immuno-oncology therapeutic candidate, CB-1158, at the 2015 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston, Massachusetts (Press release, Calithera Biosciences, NOV 6, 2015, View Source;p=RssLanding&cat=news&id=2107977 [SID:1234508339]). CB-1158 is a first-in-class immuno-oncology metabolic checkpoint inhibitor targeting arginase, a key immunosuppressive enzyme that limits T-cell proliferation in a wide range of tumors.
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"We believe that drugs targeting metabolic checkpoints have the potential to be transformational in the treatment of cancer. At Calithera, we are dedicated to researching and developing first-in-class therapies that could significantly advance the field of oncology. We have made significant progress on our CB-1158 program and remain on track to file an Investigational New Drug application (IND) in the first half of 2016," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera.
Preclinical data will be presented in a poster titled, "CB-1158 Inhibits the Immuno-Oncology Target Arginase and Causes an Immune Mediated Anti-Tumor Response," (Abstract #A195). CB-1158, a highly selective, orally bioavailable, small molecule inhibitor of human arginase with nanomolar potency, demonstrated single agent efficacy in animal models. Inhibition of tumor growth was accompanied by a rapid increase in the local concentration of arginine, and the induction of multiple pro-inflammatory changes in the tumor microenvironment. CB-1158, when administered with anti-CTLA-4, increased CD8+ T-cell infiltrates in the tumor. The addition of CB-1158 to anti-CTLA-4 and anti-PD-1, significantly inhibited tumor growth in a mouse model that was resistant to dual checkpoint inhibitor therapy. CB-1158 was well tolerated as a single agent and in combination with checkpoint inhibitors in animal studies.
Arginase is a critical immunosuppressive enzyme responsible for T-cell suppression. Arginase depletes arginine, a nutrient that is critical for the activation, growth and survival of the body’s cancer-fighting immune cells, known as cytotoxic T-cells. Arginase inhibitors can restore arginine levels and reverse this immunosuppressive effect of myeloid-derived suppressor cells (MDSCs). Myeloid cells are present in many human tumors and are correlated with poor prognosis. CB-1158 has the potential for anti-tumor activity in renal cell cancer, breast cancer, non-small cell lung cancer, acute myeloid leukemia, and other tumor types where arginase-secreting MDSCs are known to play an immunosuppressive role.